Ward 86 Management Recommendations

We concur with the treatment recommendations published by the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America (CDC/NIH/HIVMA Guidelines) for latent Mycobacterium tuberculosis infection and drug-susceptible tuberculosis (see Tables 1-3 below).(1) However, we also recommend that a local tuberculosis expert always be consulted for advice regarding which agents to use and whether dosing modifications are indicated owing to drug-drug interactions in the following situations: (In the United States, all local health departments either have staff members who can answer these questions or they can refer providers to the appropriate state or CDC tuberculosis expert.)

Patients known or suspected to have drug-resistant tuberculosis.

Patients with pericardial or central nervous system tuberculosis (in which concomitant corticosteroid therapy is indicated).

Patients for whom antiretroviral agents they are currently receiving are contraindicated with concomitant rifampin or rifabutin.

Patients receiving concomitant medications for hepatitis C infection.

Timing of initiating antiretroviral therapy (ART) in patients with tuberculosis: There are competing risks in the timing of initiating ART in HIV patients with tuberculosis. Earlier ART initiation increases the risks of adherence difficulties and immune reconstitution inflammatory syndrome (IRIS), and later initiation increases the risks of AIDS-related opportunistic infections and mortality. A series of randomized trials have clarified optimal timing of initiating ART as follows.(2,3,4)

ART should be started within 2 weeks of initiating antimycobacterial therapy for tuberculosis in patients who have an absolute CD4 count of <50 cells/µL, except for those with tuberculous meningitis in whom a full 2 weeks of antimycobacterial therapy should be administered before ART is initiated.

ART should be started between 2 weeks and 2 months of initiating antimycobacterial therapy for tuberculosis in all other patients, even those whose CD4 cell counts are in the normal range.

All commonly used NRTIs (eg, tenofovir, abacavir, lamivudine, emtricitabine) can be coadministered with rifampin or rifabutin at standard dosages. The combination of rifampin and zidovudine should be avoided because rifampin can lower zidovudine levels.

Nonnucleoside reverse transcriptase inhibitor (NNRTI) interactions:

Rifampin may cause reductions in serum NNRTI levels. Efavirenz is preferred to nevirapine given concerns about suboptimal HIV outcomes with nevirapine when is coadministered with rifampin. Data do not support weight-based dosage adjustment of efavirenz when it is coadministered with rifampin. Rifampin should not be coadministered with etravirine or rilpivirine.

Rifabutin metabolism is accelerated by efavirenz; hence, the rifabutin dosage should be increased to 450-600 mg daily if efavirenz is coadministered. If rifabutin is coadministered with rilpivirine, the rilpivirine dosage should be increased to 50 mg daily. Rifabutin can be coadministered with etravirine or nevirapine at standard dosages.

Protease inhibitor (PI) interactions:

Rifampin substantially reduces blood levels of antiretroviral PIs and should not be coadministered with PIs.

Rifabutin levels are increased to a variable degree with PI coadministration. If coadministration of rifabutin and a PI is necessary, the rifabutin dosage, if given daily, should be reduced to 150 mg daily. Patients receiving a rifabutin/PI combination should be monitored for toxicity (particularly iritis), and monitoring rifabutin serum concentrations may be considered, as patients may be at risk of acquired rifamycin resistance if rifabutin levels are subtherapeutic.

Integrase inhibitor (II) interactions:

Rifampin can be coadministered with raltegravir if the raltegravir dosage is increased to 800 mg BID, and Phase II data suggest that raltegravir 400 mg BID may be acceptable with rifampin coadministration as well; a confirmatory Phase III study is under way.(2) Rifabutin can be administered with raltegravir at standard dosages.

Dolutegravir 50 mg BID can be coadministered with rifampin.(5) Dolutegravir 50 mg daily can be coadministered with rifabutin.

Initiation of ART in patients with clinical or subclinical tuberculosis may be complicated by IRIS. For recommendations regarding tuberculosis IRIS, see section on Diagnosis and Management of Immune Reconstitution Inflammatory Syndrome.

Rifabutin (RFBT)
Rifabutin is not recommended in patients receiving Stribild and should be avoided in patients receiving protease inhibitors; if coadministration of RFBT and a protease inhibitor is necessary, the RFBT dosage, if given daily, should be reduced to 150 mg

5 mg/kg (usual dose 300 mg; however, 150 mg if given with a protease inhibitor)

5 mg/kg (usual dose 300 mg)

with EFV

450-600 mg

450-600 mg

Pyrazinamide (PZA)(weight-based dosing)

45-55 kg

1,000 mg (18.2-25.0 mg/kg )

1,500 mg (27.3-37.5 mg/kg)

56-75 kg

1,500 mg (20.0-26.8 mg/kg)

2,500 mg (33.3-44.6 mg/kg)

76-90 kg

2,000 mg (22.2-26.3 mg/kg)

3,000 mg (33.3-39.5 mg/kg)

>90 kg

2,000 mg

3,000 mg

Ethambutol (EMB)(weight-based dosing)

45-55 kg

800 mg

1,200 mg

56-75 kg

1,200 mg

2,000 mg

76-90 kg

1,600 mg

2,400 mg

About This Series

This series offers clinical practice recommendations for management of HIV-related conditions from the Ward 86 staff of the Positive Health Program at San Francisco General Hospital. Learn more.